We have described an autosomal dominant syndrome that we call ?Sensory Overstimulation Syndrome? (SOS). The most distinctive feature is the relative ineffectiveness of the local anesthetic lidocaine, a drug that blocks sodium channels. The 3 other key findings, based on characterization of 180 patients, are inattention, painful muscle cramps, and in females, severe Premenstrual Syndrome (PMS). We estimate that SOS affects 3% of the entire population, or ~9 million people in the USA, which would make this syndrome among the most frequent causes of each of these diverse findings, providing a genetic diagnosis for many who had previously been given non-syndromic diagnoses such as ADHD or PMS. We have developed a biological test kit for the lidocaine ineffectiveness that is simple, non-invasive, not painful, and non- gameable by people who are normal but trying to obtain drugs of abuse. The diagnostic test kit prototype has been tested in a small study (n=19). It has been protected with a patent filing and the FDA has asked us to validate the test kit in controlled trials before filing for marketing approval. The importance of this test goes beyond a reaching a correct diagnosis and selecting alternate local anesthetics. SOS patients with inattention respond well to potassium treatments, reducing the need for stimulants. We expect impact on drug abuse, premenstrual syndrome, and severe pain due to dental treatment in people with lidocaine ineffectiveness, often dismissed as if it were due to ?dental anxiety?. We propose the following: Aim 1: Assess reliability of taste-based lidocaine test kit in a controlled trial and compare to lidocaine injection. The ability of lidocaine oral gel to block taste (salt and sucrose solutions) will be assessed in 10 adults and then 10 teenagers, half each with history of lidocaine ineffectiveness. The painless taste-based lidocaine test will be evaluated in a randomized controlled trial, tested 4 times on different days for each subject to determine the reproducibility. At the FDA's request, each subject will also have the ?gold standard? of injection of lidocaine, assessed using pain, for comparison. Aim 2: Use the test kit to determine the prevalence of lidocaine ineffectiveness in the general population. We will use the test kit to determine the prevalence of lidocaine ineffectiveness by studying 100 individuals ages 13-49 with no diagnosis of inattention to characterize the prevalence in the general population (expect ineffective in ~2%). Aim 3: Use the test kit to determine the prevalence of lidocaine ineffectiveness in patients with ADHD. Using the test kit, we will test the association between lidocaine ineffectiveness and inattention by studying 80 individuals ages 13- 49 with inattention, chosen from those who had been diagnosed with ADHD (expect ineffective in ~30%). We expect that this lidocaine test will provide a mechanistic biomarker for identification of the SOS syndrome in significant fractions of people currently diagnosed as having ADHD or PMS. Given the apparent high prevalence of SOS, the potential of the lidocaine taste test kit for commercialization is high, as is the impact on public health.